Abnormal Uterine Bleeding: Etiology, Evaluation and End-points for the Non-gynecologist

Kelly A. Best, MDAbstract: Abnormal uterine bleeding is an extremely common complaint in the primary care providers oce. Critical in the initial evaluation of abnormal uterine bleeding is a detailed history of the pattern of bleeding including timing, duration, quantity and other associated factors. The work-up of abnormal uterine bleeding can often seem daunting, but using the reproductive age of the patient as a guide can often simplify the process. In addition, both medical and surgical options exist for the successful and cost-eective treatment of AUB. This article will review the etiology of AUB as well as provide a guide for the stepwise evaluation of the patient with abnormal uterine bleeding and discuss the options available in the management of this condition. Abnormal uterine bleeding is a common complaint among patients in the primary practice setting. One study found that menstrual complaints accounted for 19.1 percent of the 20.1 million visits to physician oces over a two-year period.1 In addition, an estimated 25 percent of gynecologic surgeries involve the diagnosis of abnormal uterine bleeding.2 This article presents a brief discussion on the etiology of abnormal uterine bleeding, the process of evaluation, and a review of both medical and surgical management options. The intervals, duration and volume of menstrual ow remain relatively stable during a womans reproductive years. During the follicular phase of the cycle, follicle stimulating hormone levels rise, producing a dominant follicle to mature and produce estrogen. As estrogen levels rise, menstrual ow ceases and the endometriun proliferates. Lutenizing hormone levels rise as a result of increased estrogen, and ovulation occurs. The luteal phase is characterized by progesterone production by the corpus luteum allowing for a cessation of endometrial proliferation and a subsequent dierentiation. If fertilization does not occur, progesterone levels fall and endometrial shedding occurs.3 Abnormal uterine bleeding may take many forms from infrequent episodes, excessive ow, prolonged duration and intermenstrual bleeding. Critical to the evaluation of the cause is a methodical history to include the usual menstrual pattern, the recent bleeding pattern and timing, sexual activity, recent trauma, and systematic review to rule out infection or systemic diseases (See Table 1). In addition, a careful review of the patients current medications should be performed. Specically, selective serotonin reuptake inhibitors, antipsychotics, corticosteroids, anticoagulants, hormonal supplements, as well as herbalsAddress Correspondance to: Kelly A. Best, MD, Clinical Assistant Professor and Obstetrician/Gynecologist, University of Florida Health Sciences Center, Jacksonville, FL. Email: Kelly.best@jax. u.edu. www . DCMS online . org

Table 1 Terminology Used to Describe Abnormal Uterine Bleeding

TermMenorrhagia Metrorrhagia

DenitionProlonged or excessive bleeding at regular intervals Irregular, frequent bleeding of varying amounts but not excessive

Menometrorrhagia Prolonged or excessive bleeding at irregular intervals Polymenorrhea Amenorrhea Oligomenorrhea Intermenstrual Regular bleeding at intervals of less than 21 days No uterine bleeding for at least 6 months Bleeding at intervals greater than every 35 days Uterine bleeding between regular cycles

including soy, ginkgo and ginseng may cause changes in menstrual patterns.4 A pregnancy test is often the initial step in the evaluation of abnormal uterine bleeding in the reproductive age woman. Causes of pregnancy-related bleeding include miscarriage, placenta previa, placental abruption, ectopic pregnancy or trophoblastic disease. A detailed pelvic examination should include an examination of the lower genital tract for vulvar, vaginal, or cervical pathology (including Papanicolaou testing), trauma and infection. The bimanual exam may reveal an enlarged, irregularly shaped (broid) or tender uterus (adenomyosis). Systemic disease should also be considered in the reproductive age and perimenopausal women who presents with abnormal uterine bleeding. Thyroid dysfunction, hematologic disorders, hepatic or adrenal dysfunction, and pituitary/ hypothalamic disorders should be considered (See Table 2, next page).5 Adolescent patients should have a coagulation prole to evaluate for the risk of coagulopathies such as von Willebrands disease. Transvaginal ultrasonography or sonohysterography is useful in the evaluation of abnormal uterine bleeding in the setting of enlarged uterus, adnexal pathology or a normal pelvic examination (in the case of submucosal broids or polyps). Dysfunctional uterine bleeding (DUB) is a diagnosis of exclusion and refers to uterine bleeding not related toNortheast Florida Medicine Vol. 57, No. 2 2006 27

architectural abnormalities such as broids or polyps, and characterized by irregular, prolonged and often heavy bleeding episodes. DUB is common in the post-menarche period due to immaturity of the hypothalamic-pituitary-ovarian axis and in perimenopause secondary to declining estrogen levels (and hence failure of the LH surge) and is commonly anovulatory in nature. Other causes of anovulatory bleeding include: exercise, stress, eating disorders, polycystic ovarian syndrome, and thyroid disease.6 (See Chart 1, next page) The risk of developing endometrial carcinoma increases with age. The incidence doubles from 2.8 cases per 100,000 in the 30-34 year age group to 6.1 cases per 100,000 in those aged 35-39. In women 40-49 years, the incidence of endometrial carcinoma is 36.5 cases per 100,000. The American College of Obstetricians and Gynecologists recommends endometrial sampling in women 35 years and over with abnormal uterine bleeding.7 In-oce endometrial biopsy is a safe, sensitive method to exclude endometrial carcinoma in this population. Women determined to be at low risk for endometrial carcinoma may initially attempt medical management; however, endometrial biopsy in combination with pelvic sonogram or saline infusion sonohysterography is recommended in the evaluation of abnormal uterine bleeding in premenopausal woman at high risk for endometrial carcinoma or in the postmenopausal woman with abnormal uterine bleeding.8 (See Chart 2, next page) Although dilation and curettage has been the gold standard for the diagnosis of endometrial cancer, it is not considered therapeutic for abnormal uterine bleeding.9 The addition of hysteroscopy is critical in the complete evaluation of the endometrial cavity often permitting the diagnosis (and treatment) of polyps and submucous broids. About 30% of women will be diagnosed with broids in their lifetime. Up to 80% of broids are asymptomatic (likely28 Vol. 57, No. 2 2006 Northeast Florida Medicine

intramural or pedunculated in location) and therefore not likely to require treatment. The rationale for treatment should consider the degree of symptoms (pain, pressure, bleeding, anemia), desire for fertility, co-morbid medical conditions and proximity to menopause.10 Endometrial polyps are localized overgrowths of the endometrium that project into the uterine cavity. Such polyps may be sessile or pedunculated and rarely include areas of neoplasia. The most frequent symptom of women with endometrial polyps is metrorrhagia followed by menorrhagia, post-menopausal bleeding, and breakthrough bleeding during hormonal therapy. Overall, endometrial polyps account for 25% of abnormal bleeding in both premenopausal and postmenopausal women. In the absence of uterine pathology, medical management is preferred over surgical options as initial treatment. In the reproductive age woman who is not pregnant and has an otherwise normal physical exam without evidence of systemic disease, abnormal uterine bleeding is often anovulatory in nature and can be managed with hormonal manipulation. Oral contraceptive pills, patches or vaginal rings will often regulate the menstrual cycle as well as provide protection against long-term eects of chronic anovulation as in the polycystic ovarian syndrome (PCOS) patient. Additionally, cyclic progestins or levonorgestrel IUD may also be utilized to regulate the menstrual cycle in this population. Table 3 provides an overview of the agents most commonly utilized in the medical management of abnormal uterine bleeding.11 (See Table 3, p. 30) Surgical management may be required when medical management fails or is contraindicated such as in the case of adenocarcinoma. Dilation and curettage is the treatment of choice for women with acute hemorrhage and hypovolemia but should not be relied upon for long-term success as the pathophysiologic root cause remains unchanged. In womenwww . DCMS online . org

Chart 1 Work-up of Reproductive Age Women with AUB

who have completed childbearing, surgical options for the management of abnormal uterine bleeding include operative hysteroscopy for the removal of polyps and submucosal broids, endometrial ablation, uterine artery embolization in the broid uterus and hysterectomy. A broad spectrum of ablative techniques has been developed to avoid the morbidity of hysterectomy. These techniques can be divided into hysteroscopic and non-hysteroscopic techniques and include: Nd:YAG laser, electrosurgery (rollerball, resection), heated saline, balloon, cryotherapy, bipolar radiofrequency probe, and microwave. Comparative amenorrheawww . DCMS online . org

and success rates (dened as percentage of patients satised with the post-procedure reduction in bleeding) reported for endometrial ablation rangefrom 67-96% at 1-3 years depending on the technique. Thus, when bleeding is the sole problem (no anatomic distortions or pain involved), ablation oers a very attractive alternative to hysterectomy as many insurance companies will no longer cover a hysterectomy for bleeding if ablation has not been attempted rst. Denitive surgical management in the form of hysterectomy is often the end point in the management of abnormal uterine bleeding following failed medical management, bleeding dueNortheast Florida Medicine Vol. 57, No. 2 2006 29

Table 3 Medical Management of Abnormal Uterine Bleeding

Estrogens Acute bleed 2.5mg QID orally, if not controlled in 24 hours can increase to 5mg QID (alternatively can give 25 mg IV q4 hours x 24 hours) After acute bleed, continue oral estrogen and add MPA 10mg qday for 7-10 days Alternatively can use monophasic OC 50g E/P four times daily for one week Oral contraceptives Long term management Begin 20g. May be contraindicateed in women over 35 years who smoke 10 mg daily for 10 days each month

Intrauterine device placed after ruling out pregnancy 5 year use

to organic causes, or secondary to adenocarcinoma. The decision to perform a hysterectomy should be reached on an individual basis and issues relating to preoperative risk, pelvic support, ovarian conservation, sexual function, future cervical/vaginal cytologic screening, and operative technique should be discussed in detail with a gynecologist early in the process.

The diagnostic approach to abnormal uterine bleeding on the surface can seem daunting. Combined with a detailed history and physical exam the etiology often can be narrowed. The history should elicit information regarding the timing, frequency, duration and amount of bleeding as well as a sexual history, previous gynecologic history,assessment for risk of pregnancy, medication use or discontinuation and a general medical history. The physical exam should focus on the pelvic organs as well as an evaluation for signs of medical conditions such ashypothyroidism, liver disease or coagulopathy.Using the reproductive age as a guide, a logical and cost-eective diagnostic evaluation should be conducted starting with a pregnancy test (when appropriate) and other appropriate laboratory studies. Transvaginal ultrasound (or sonohysterography) coupled with endometrial biopsy (in women at high risk for endometrial carcinoma) is useful in the evaluation ofabnormal uterine bleeding when the history and physical suggests an anatomic or structuralcause. Medical management isconsidered rstline in the treatment of abnormal uterine bleeding. Oral contraceptive pills, patches, vaginal rings, cyclic progestins or levonorgestrel IUD may be utilized to regulatemenses. When medical management fails, surgical options that may be considered include operative hysteroscopy with endometrial resection,endometrial ablation, uterine artery embolization or hysterectomy.Early referral to a gynecologist can assist in choosing the most effective means for the management of many of the causes of abnormal uterine bleeding.